Persistence of a Liver Metabolic Zonation in Extra-Hepatic Biliary Atresia Cirrhotic Livers

Abstract

ABSTRACT. To evaluate whether liver metabolic zonation persists in human biliary cirrhosis, we used quantitative cytochemistry to measure activities of glucose 6 phosphatase (G6P) and NADPH dehydrogenase (ND) in hepatocytes situated in different zones of liver cirrhotic nodules. Liver specimens were obtained from 13 children with extrahepatic biliary atresia with compensated cirrhosis. Activity and distribution were compared with zonal activities measured in 17 control human liver specimens obtained during reduction hepatectomies for orthotopic liver transplantation. In normal human liver, G6P was 1.86 times more active in the periportal than in the perivenular zone. On the contrary, ND activity was lower in the periportal zone (63% of perivenular activity). A metabolic zonation persisted in extra-hepatic biliary atresia with compensated cirrhosis. G6P activity was 1.56 times greater at the nodule periphery than at the nodule center, whereas ND activity was lower at the periphery (75% of nodule center activity). This metabolic zonation is the opposite of that observed in animal toxic (CCL,) cirrhosis, in which greater G6P activity is observed at the nodule center and greater ND activity at its periphery. This confirms our previous hypothesis that the type of cirrhotic metabolic zonation may depend on the site of initial liver damage. (Pediatr Res 30: 286-289, 1991)

Continuous increase of alcohol dehydrogenase activity along the liver plate in normal and cirrhotic human livers

“…Higher ADH activity has also been measured in juvenile rats compared with mature ones (4). The zonal distribution of ADH in the cirrhotic nodules is in accordance with our previous demonstration, which showed that in biliary type cirrhosis, perivenular-like activity is observed at the centers of the cirrhotic nodules, and periportal-like activity is observed at the periphery of these nodules (26,27). Because ADH was most active at the centers of the cirrhotic nodules, alcohol-related liver damage could be more important in this zone of these patients in the event of future drinking habits.…”

Anatomy, pathophysiology and basic mechanisms of disease

“…672 Indeed, the development of penetrating afferent vessels can lead to outright reversal of blood flow, from the centre of parenchymal nodules to the periseptal periphery, which is contrary to what one might expect. 672 In human studies, reversal of zonation does not appear to occur in biliary cirrhosis, 677,679,680 and the overall metabolic organization of the acinus is either retained or 'flattened' in cirrhosis from chronic viral hepatitis or alcoholic liver disease, with no zonation at all observed for hepatocellular enzymatic activities. 681 An enzyme with a distribution that is almost exclusively perivenular (and restricted to the layer of two to four hepatocytes around the terminal hepatic vein) is glutamine synthetase.…”

Liver metabolic zonation in rat biliary cirrhosis: Distribution is reverse of that in toxic cirrhosis

“…G6P. This medium consisted of acetate buffer (0.1 mmol/L, pH 6.5), glucose-6-phosphate (2.1 mmol/L) and PBNO, (2.4 mmol/L) (4,5,8). The reaction was carried out in a Coplin jar at 37" C and stopped after 6 min by washing the slides in distilled water.…”

“…ND. Incubation medium contained glycyl glycine buffer (50 mmol/L, pH 7.9), polyvinyl alcohol (20%), NADPH, (3 mmol/L) and nitroblue tetrazolium (4.9 mmol/L) (4,5,9). Slidemounted sections were incubated at 37" C in plastic rings for FIG.…”

“…Hepatocytes differ in their biochemical activities according to their location along the sinusoids (1,2). We previously showed that this so-called metabolic zonation is also observed in cirrhotic livers, despite the marked architectural changes of this condition (3,4). In rats intoxicated with CCl,, the zonal activity at the periphery of the cirrhotic nodules corresponded to the perivenular activity of normal controls, whereas activity at the nodule centers was similar to the periportal activity of controls (3).…”